Bioequivalence of a hybrid pegylated liposomal doxorubicin hydrochloride injection and Caelyx®: A single-dose, randomized, multicenter, open-label, two-period crossover study in patients with advanced ovarian cancer.

OBJECTIVE: To evaluate the bioequivalence of a hybrid pegylated liposomal doxorubicin (PLD) hydrochloride injection with reference product Caelyx®. METHODS: This multicenter, open-label, balanced, randomized, two-treatment, two-period, two-sequence, single-dose, crossover, bioequivalence study was conducted in female patients aged ≥18 years and ≤75 years with ovarian cancer, whose disease progressed or recurred after platinum-based chemotherapy, and who were scheduled to start PLD therapy. Patients were intravenously infused drugs over 1 h at 50 mg/m2 dose two hours after breakfast on the first day of the chemotherapy cycle in period-I and crossed over to the other arm in period-II (day 29). Pharmacokinetic (PK) analyses were performed using two separate, validated liquid chromatography-mass spectrometry methods for encapsulated and unencapsulated doxorubicin. RESULTS: Both the test and reference formulations were well-tolerated and safe. The pharmacokinetic analysis for both encapsulated and unencapsulated doxorubicin was conducted in 50 patients and PK parameters were found to be comparable between test and reference products. The geometric mean ratios (90% confidence interval) of hybrid PLD/Caelyx® were; maximum measured plasma concentration (Cmax): 91.94-97.28%, area under the plasma concentration versus time from time 0 to t (AUC0-t): 95.19-103.67%, AUC from time 0 to ∞ (AUC0-∞): 95.13-103.66% for encapsulated doxorubicin and for unencapsulated doxorubicin Cmax: 92.08-116.46%, AUC0-t: 91.91-108.28%, AUC0-∞: 93.45-110.05%. CONCLUSION: The PLD formulation was found to be bioequivalent to Caelyx®.

Fixed dose combination of capecitabine and cyclophosphamide in metastatic breast cancer: Results from THE ENCLOSE phase 2/3 randomized multicenter study.

AIM: To evaluate pharmacokinetics, efficacy and safety of fixed-dose combination (FDC) of oral capecitabine + cyclophosphamide in metastatic breast cancer (MBC) patients progressing after anthracycline and/or taxane chemotherapy. METHODS: In this prospective, adaptive, phase-2/3, open-label study (CTRI/2014/12/005234), patients were randomized (1:1:1) to three FDC doses (doses/day: D1, capecitabine + cyclophosphamide 1400 mg + 60 mg; D2, 1800 mg + 80 mg; D3, 2200 mg + 100 mg) for 14 days, in 21-day cycles. In Part-I, multiple-dose pharmacokinetics and optimal dose(s) were evaluated with futility analysis. Group(s) with <3 responders based on best overall response rate (BOR, complete response [CR]+partial response [PR]), were discontinued. Efficacy (BOR, disease control rates [DCR; CR + PR + stable disease]) and safety of optimal dose(s) were evaluated in Part-II. RESULTS: Of 66 patients (n = 22/group) in Part-I, pharmacokinetics (D1 = 7/22, D2 = 9/22, D3 = 8/22) showed dose-proportionality for cyclophosphamide and greater than dose-proportionality for capecitabine. Modified intent-to-treat (mITT) analysis showed BOR of 7.14% (1/14) in D1 (discontinued), and 22.22% (4/18) each in D2 and D3, respectively. In Part-II, 50 additional patients were randomized in D2 and D3 (n = 144; total 72 [22 + 50] patients/group). mITT analysis in D2 (n = 54) and D3 (n = 58) showed BOR of 29.63% (16/54, 95%CI: 17.45-41.81%) and 22.41% (13/58, 95%CI: 11.68-33.15%), respectively. DCR in D2 and D3 were 87.04% (47/54, 95%CI: 78.08-96.00%) and 82.76% (48/58; 95%CI: 73.04-92.48%) after 3 and 57.41% (31/54; 95%CI: 52.41-79.50%) and 50.00% (29/58; 95%CI: 40.40-67.00%), after 6-cycles, respectively. Hand-foot syndrome (16.67%), vomiting (9.72%) in D2, and hand-foot syndrome (18.06%), asthenia (15.28%) in D3 were most-common adverse events. CONCLUSION: FDC of capecitabine + cyclophosphamide (1800 + 80 mg/day) showed high disease control rates and good safety profile in MBC patients.

Efficacy and safety of nanosomal docetaxel lipid suspension based chemotherapy in metastatic ovarian carcinoma: A retrospective study.

The aim of the current study was to assess the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS) based chemotherapy in patients with metastatic epithelial ovarian carcinoma. In the present multicenter study, the medical records of patients who received NDLS (60-75 mg/m2; 3-weekly cycles) based chemotherapy for metastatic epithelial ovarian cancer in routine clinical care were retrospectively evaluated. Patients were followed-up from September 2014 until September 2018. The efficacy endpoints were the overall response rate (ORR) and disease control rate measured in accordance with the Response Evaluation Criteria in Solid Tumours 1.1. Overall survival (OS) and safety were also evaluated. Of the 13 patients evaluated, 46.2% (6/13) received NDLS-based first-line chemotherapy and 53.8% (7/13) patients received second-line chemotherapy [platinum-sensitive, 57.1% (4/7); platinum-resistant, 42.9% (3/7)]. The ORRs were 60.0% (3/5) and 57.1% (4/7) for patients receiving first- and second-line chemotherapy, respectively. The estimated median OS for patients receiving NDLS-based first-line chemotherapy was 17.4 months (follow-up duration, 4.3-49.4 months). The estimated median OS was 26.1 months (follow-up duration, 5.1-37.5 months) in patients with platinum-sensitive disease, whereas the OS was 14.8 months (follow-up duration, 3.5-14.8 months) in patients with platinum-resistant disease. No grade III/IV adverse events (AEs) were observed; ≥1 AE in grade I-II was reported in 84.6% (11/13) of patients. Overall, NDLS-based chemotherapy was efficacious and well-tolerated in the management of metastatic epithelial ovarian carcinoma.

Biweekly DoceAqualip in mCRPC patients beyond 20 cycles: A case series.

INTRODUCTION: Docetaxel 75 mg/m2 every 3 weeks for up to 10 cycles is an accepted standard regimen in metastatic castration-resistant prostate cancer (mCRPC). We report our experience with >20 cycles of biweekly nanosomal docetaxel lipid suspension (NDLS) treatment in patients with mCRPC. CASE REPORTS: Cases with long-term treatment of NDLS treatment in mCRPC patients were identified from the medical records of Jawaharlal Nehru Cancer Hospital & Research Centre Bhopal, India. A total of three cases with >20 cycles of NDLS are presented here. MANAGEMENT AND OUTCOMES: Overall, the 3 patients received biweekly NDLS at a dose of 45 mg/m2 for 22, 36, and 40 cycles, respectively, except for one patient where NDLS was initiated at 50 mg/m2 and later reduced to 45 mg/m2. All the 3 patients reported prostate-specific antigen (PSA) response (>50% decline in PSA levels from baseline). The time to treatment failure (TTF) was 14.8, 18.2, and 20.6 months in these 3 patients, respectively. PSA nadir occurred after 14, 6 and 13 cycles, respectively. The OS was 21.6, 22.2 and 25.8 months, respectively. Anemia, lymphopenia, and neutropenia were the most common adverse events. NDLS treatment was overall well-tolerated without any new safety concerns. CONCLUSIONS: Biweekly NDLS for >20 cycles was effective and well-tolerated in patients with mCRPC. NDLS can potentially be used for long-term management, which may be a requirement for most patients with mCRPC.

A Multicentric, Retrospective Efficacy and Safety Study of Nanosomal Docetaxel Lipid Suspension in Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: To evaluate the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS, DoceAqualip) in patients with metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS: In this multicenter, retrospective study, we analyzed the medical charts of mCRPC patients, who were treated with NDLS administered as 2-weekly (50 mg/m2) or 3-weekly regimens (75 mg/m2). The study endpoints were prostate-specific antigen (PSA) response (>50% PSA decline from baseline), PSA progression (PSA increase from baseline beyond 12 weeks: ≥25% and ≥2 ng/mL), median PSA decline, and time-to-treatment failure (TTF). Overall survival (OS) and safety were also evaluated. RESULTS: Data of 24 patients with mCRPC were analyzed in this study. NDLS was administered as a 2-weekly regimen in 37.5% (9/24; all first-line) patients and as a 3-weekly regimen in 62.5% patients (15/24; first-line: 20% (3/15), second-line: 80% (12/15)). Overall, PSA response was reported in 66.7% (16/24) patients. The PSA response was 77.8% (7/9 patients) in the 2-weekly group and 60% (9/15 patients) in the 3-weekly group. The median decline in PSA was 96.31% in the 2-weekly group and 83.29% in the 3-weekly group; the median TTF was 6.7 and 6.5 months in the 2 weekly group and 3-weekly group, respectively. The median OS was 14.6 months (follow-up: 5.5-25.8 months) in the 2-weekly group whereas it was not reached in the 3-weekly group (follow-up: 7.9-15.6 months). The most common hematological AEs were anemia, lymphopenia, thrombocytopenia, and neutropenia whereas nausea, weakness, constipation, vomiting, and diarrhea were the most common (≥10%) nonhematological AEs. Overall, NDLS treatment was well tolerated without any new safety concerns. CONCLUSIONS: Nanosomal docetaxel lipid suspension (2-weekly or 3-weekly) was effective and well tolerated in patients with metastatic castration-resistant prostate cancer.

Efficacy and safety of nanosomal docetaxel lipid suspension-based chemotherapy in squamous cell carcinoma of the head and neck: A multicenter retrospective study.

Squamous cell carcinoma of the head and neck (SCCHN) is the most common cancer in Indian men. Docetaxel alone or in combination with other chemotherapeutic agents is recommended for the management of SCCHN. The present multicenter, retrospective study was conducted to evaluate the efficacy and safety of a novel docetaxel formulation 'nanosomal docetaxel lipid suspension (NDLS)'-based chemotherapy in SCCHN. The medical records of patients with SCCHN, who were treated with NDLS-based chemotherapy and followed up between August 2014 and September 2018, were reviewed. The efficacy endpoints were overall response rate [ORR; complete response (CR) + partial response (PR)] and disease control rate (DCR; CR + PR + stable disease) for patients receiving NDLS-based induction or palliative chemotherapy. Overall survival (OS) and safety were also evaluated. Efficacy evaluation was available in 30/34 patients (induction, 20/23; palliative, 10/11). NDLS-based induction chemotherapy showed an ORR and DCR of 95% and a median OS of 43.5 months (follow-up duration, 0.6-80.3 months). For NDLS-based palliative chemotherapy, the ORR and DCR were 50% and the median OS time was 4.6 months (follow-up duration, 1.8 to 14.3 months). At least one adverse event was reported in 82.6% patients. No new safety concerns were reported. Overall, NDLS-based chemotherapy was effective and well tolerated in the treatment of SCCHN.

Nanosomal Docetaxel Lipid Suspension-Based Chemotherapy in Breast Cancer: Results from a Multicenter Retrospective Study.

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS, DoceAqualip)-based chemotherapy in breast cancer. METHODS: Medical charts of patients with breast cancer, who were treated and followed up with NDLS (75-100 mg/m2; 3-week cycle)-based chemotherapy from August 2014 to September 2018, were analyzed in this multicenter, retrospective study. The study endpoints were overall response rate (ORR: complete response [CR]+partial response [PR]) and disease control rate (DCR: CR+PR+stable disease [SD]) in neoadjuvant and metastatic settings. Overall survival (OS) and safety were evaluated for all settings. RESULTS: Of 91 patients (neoadjuvant: 12, adjuvant: 61, metastatic: 18), efficacy evaluation in 29 patients (neoadjuvant: 12/12, metastatic: 17/18) demonstrated an ORR and DCR of 100%, respectively, in the neoadjuvant setting, and an ORR of 64.7% and DCR of 70.6%, respectively, in the metastatic setting. At a median follow-up of 21.6 months (range: 2.1 to 49.9 months), median OS was not reached in neoadjuvant and adjuvant settings, and it was 30.4 months in metastatic settings. At least one adverse event (AE) was reported in 59.3% of patients. Anemia, thrombocytopenia, lymphopenia, and neutropenia were the most common hematological AEs reported while hyperglycemia and alteration in liver function tests were the most common non-hematological AEs. NDLS-based treatment was well tolerated without any new safety concerns. CONCLUSION: Nanosomal docetaxel lipid suspension-based chemotherapy was efficacious and well tolerated in the treatment of breast cancer. Further, NDLS is being evaluated prospectively in patients with triple-negative breast cancer (ClinicalTrials.gov: NCT03671044).

Nanosomal docetaxel lipid suspension based chemotherapy in a pregnant MBC patient - a case report.

The current report presents a case of a pregnant woman with breast cancer metastasized to liver and lungs. The standard of care for breast cancer in pregnancy is anthracycline/taxane-based chemotherapy regimens. Docetaxel has shown a favorable toxicity profile during the second and third trimesters of pregnancy. A novel nanosomal docetaxel lipid suspension (NDLS) (DoceAqualip), with a proven efficacy and tolerability profile, has been approved in India for the treatment of advanced solid tumors since 2013. We present here a case of a pregnant woman with metastatic breast cancer managed with NDLS based TAC regimen showing a partial response after six cycles. The patient delivered a healthy male child with normal Apgar score and weight at the 32nd week of gestation.

Management of primary squamous cell carcinoma of the pancreas with a nanosomal paclitaxel lipid suspension-based regimen: A case report.

Squamous cell carcinoma (SCC) of the pancreas is a rare tumor with only a few case reports available. It is an aggressive form of pancreatic cancer with a poor prognosis. The diagnosis and optimal management of SCC of the pancreas is poorly defined due to the lack of standard treatment or guidelines and owing to the rarity of this malignancy. Patients suffering from SCC of the pancreas do not respond well to chemotherapy or radiotherapy and isolated reports are available on the use of gemcitabine and newer taxane formulations. Surgical resection of the tumor is the most effective modality; however, due to a delay in diagnosis, the majority of pancreatic SCCs remain unresectable. Herein, a case of SCC of the pancreatic tail is reported in a 60-year-old patient who was managed with a combination of albumin-free nanosomal paclitaxel lipid suspension (NPLS) and gemcitabine in a neoadjuvant setting. To the best of our knowledge, this is the first such case report of a locally advanced SCC of the pancreatic tail showing an overall survival of 1 year following treatment with an NPLS based regimen. The treatment was well tolerated with no serious safety concerns.

Real-Life Clinical Effectiveness of Razumab® (the World's First Biosimilar of Ranibizumab) in Retinal Vein Occlusion: A Subgroup Analysis of the Pooled Retrospective RE-ENACT Study.

BACKGROUND: This subgroup analysis of the RE-ENACT study evaluates the effectiveness of Razumab® (the world's first biosimilar of ranibizumab by Intas Pharmaceuticals Ltd.) in Indian patients with retinal vein occlusion (RVO). METHODS: The data on patients with RVO who had received ≥3 injections of Razumab® between January and August 2016 were analyzed. Endpoints were: improvement in best corrected visual acuity (BCVA), and a decrease in central macular thickness (CMT), intraretinal fluid (IRF), and subretinal fluid (SRF) from baseline at weeks 4, 8, and 12. RESULTS: Of 160 patients, the majority (61.87%) were men. The mean (±SE) BCVA improved from baseline (0.76 ± 0.04) to week 4 (0.73 ± 0.03; p = 0.0656), which attained significance at week 8 (0.55 ± 0.02; p < 0.0001) and week 12 (0.47 ± 0.02; p < 0.0001). The mean (±SE) CMT significantly decreased from baseline (447.60 ± 10.91 µm) to week 4 (431.84 ± 10.92 µm; p = 0.0028), week 8 (339.28 ± 8.12 µm; p < 0.0001), and week 12 (298.23 ± 6.68 µm; p < 0.0001). The proportion of patients with IRF and SRF significantly (p < 0.0001) decreased from baseline to weeks 4, 8, and 12 (IRF: from 70.63 to 45.63, 39.38, and 30.00%, respectively; SRF: from 65.63 to 37.50, 28.13, and 24.38%, respectively). A subgroup analysis of branch RVO and central RVO showed similar results. No new safety concerns were observed. CONCLUSION: Razumab® (biosimilar of ranibizumab) effectively improved visual acuity and disease outcomes in patients with RVO in a real-world setting with no new safety concerns.

Efficacy and safety of DoceAqualip in a patient with locally advanced cervical cancer: A case report.

The standard of care for locally advanced cervical cancer has been the combination of a taxane with platinum based therapy. Conventional docetaxel is known to cause hypersensitivity reactions, fluid retention and other toxicities due to polysorbate-80 and ethanol. Corticosteroid premedication prior to docetaxel administration is required to prevent these toxicities, however, toxicities are still observed, sometimes fatal, despite premedication. DoceAqualip, a nanosomal docetaxel lipid suspension, developed with lipids generally regarded as safe (GRAS) by the US Food and Drug Administration, is devoid of polysorbate-80 and ethanol. DoceAqualip has been demonstrated to be effective and well-tolerated in various cancer types. The authors' report a case of a patient with Stage IIIB cervical cancer who was treated with carboplatin and DoceAqualip (concurrent ChemoRT) and achieved complete response without any serious adverse events.

Doceaqualip in a patient with prostate cancer who had an allergic reaction to conventional docetaxel: A case report.

Docetaxel has been widely used in the treatment of several cancers, including adenocarcinoma of the prostate gland. As docetaxel is insoluble in water, it must be administered with polysorbate 80 and ethanol, which are known to cause hypersensitivity reactions. Premedication with corticosteroids and antihistamines is advocated prior to docetaxel administration; however, toxicities, occasionally fatal, have been reported, even with corticosteroid premedication. We herein report the case of a patient with adenocarcinoma of the prostate, with bone metastasis and an Eastern Cooperative Oncology Group performance status of <2, who developed an allergic reaction to conventional docetaxel (Taxotere), despite being premedicated with corticosteroids and antihistamines. The patient was managed with corticosteroids and antihistamines, and was later started on Doceaqualip, a nanosomal docetaxel lipid suspension. Doceaqualip was well-tolerated by the patient and 5 cycles were subsequently administered, without any adverse reactions. Adenocarcinoma also regressed, as evidenced by positron emission tomography/computed tomography.